Which drugs should post-MI patients routinely receive?

patients should be placed on the following medications: antiplatelet agents (strength of recommendation [SOR]: A, meta-analysis for aspirin; A, multiple randomized controlled trials [RCTs] for aspirin plus clopidogrel) a statin; atorvastatin has the best evidence (SOR: B, a single RCT) a beta-blocker (SOR: A, meta-analysis) renin-angiotensin-aldosterone system blockers, whether or not the ejection fraction is diminished after myocardial infarction (MI) (SOR: A, meta-analysis for angiotensin-converting enzyme [ACE] inhibitor; B, single RCT for ACE inhibitor plus aldosterone blocker)

What's the best drug treatment for premature ejaculation?

Antidepressants--specifically clomipramine, fluoxetine, paroxetine, and sertraline--are best and have been shown to improve symptoms of premature ejaculation (strength of recommendation [SOR]: A, meta-analysis of randomized controlled trials [RCTs]). The topical application of prilocaine-lidocaine cream (trade name EMLA) improves intravaginal ejaculatory latency time (IELT), but penile numbness and loss of erection may occur (SOR: B, based on several small RCTs)

International variation in outcomes among people with cardiovascular disease or cardiovascular risk factors and impaired glucose tolerance: insights from the NAVIGATOR Trial

Background: Regional differences in risk of diabetes mellitus and cardiovascular outcomes in people with impaired glucose tolerance are poorly characterized. Our objective was to evaluate regional variation in risk of new‐onset diabetes mellitus, cardiovascular outcomes, and treatment effects in participants from the NAVIGATOR (Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research) trial. Methods and Results: NAVIGATOR randomized people with impaired glucose tolerance and cardiovascular risk factors or with established cardiovascular disease to valsartan (or placebo) and to nateglinide (or placebo) with a median 5‐year follow‐up. Data from the 9306 participants were categorized by 5 regions: Asia (n=552); Europe (n=4909); Latin America (n=1406); North America (n=2146); and Australia, New Zealand, and South Africa (n=293). Analyzed outcomes included new‐onset diabetes mellitus; cardiovascular death; a composite cardiovascular outcome of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke; and treatment effects of valsartan and nateglinide. Respective unadjusted 5‐year risks for new‐onset diabetes mellitus, cardiovascular death, and the composite cardiovascular outcome were 33%, 0.4%, and 4% for Asia; 34%, 2%, and 6% for Europe; 37%, 4%, and 8% for Latin America; 38%, 2%, and 6% for North America; and 32%, 4%, and 8% for Australia, New Zealand, and South Africa. After adjustment, compared with North America, European participants had a lower risk of new‐onset diabetes mellitus (hazard ratio 0.86, 95% CI 0.78–0.94; P=0.001), whereas Latin American participants had a higher risk of cardiovascular death (hazard ratio 2.68, 95% CI 1.82–3.96; P<0.0001) and the composite cardiovascular outcome (hazard ratio 1.48, 95% CI 1.15–1.92; P=0.003). No differential interactions between treatment and geographic location were identified. Conclusions: Major regional differences regarding the risk of new‐onset diabetes mellitus and cardiovascular outcomes in NAVIGATOR participants were identified. These differences should be taken into account when planning global trials

Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity. Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively. Setting Multinational study of 9306 participants. Participants: Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme. Outcome measures: Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included. Results: Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ2=16.8; p<0.0001), but not change in weight (χ2=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ2=5.9; p=0.02) but not previous step count (χ2=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ2 for previous weight measurements 747.3; p<0.0001) and physical activity (χ2 for previous step count 432.6; p<0.0001), these effects were of limited clinical importance. Conclusions: While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables

Are Textures Natural?

We make the simple observation that, because of global symmetry violating higher-dimension operators expected to be induced by Planck-scale physics, textures are generically much too short-lived to be of use for large-scale structure formation.Comment: 9p

Absolute-Frequency Measurement of the Iodine-Based Length Standard at 514.67 nm

The absolute frequency of the length standard at 514.67 nm based on the molecular iodine (127I 2) transition of the P(13) 43-0 component a3 is measured using a self-referenced femtosecond optical comb. This frequency-based technique improves measurement precision more than 100 times compared with previous wavelength-based results. Power- and pressure-related frequency shifts have been carefully studied. The measured absolute frequency is 71.8±1.5 kHz higher than the internationally accepted value of 582490603.37±0.15 MHz, adopted by the Comité International des Poids et Mesures (CIPM) in 1997

Orbital Orientations of Exoplanets: HAT-P-4b is Prograde and HAT-14b is Retrograde

We present observations of the Rossiter-McLaughlin effect for two exoplanetary systems, revealing the orientations of their orbits relative to the rotation axes of their parent stars. HAT-P-4b is prograde, with a sky-projected spin-orbit angle of λ = –4.9 ± 11.9 deg. In contrast, HAT-P-14b is retrograde, with λ = 189.1 ± 5.1 deg. These results conform with a previously noted pattern among the stellar hosts of close-in giant planets: hotter stars have a wide range of obliquities and cooler stars have low obliquities. This, in turn, suggests that three-body dynamics and tidal dissipation are responsible for the short-period orbits of many exoplanets. In addition, our data revealed a third body in the HAT-P-4 system, which could be a second planet or a companion star

Risk of anemia with metformin use in type 2 diabetes:A MASTERMIND study

Objective: To evaluate the association between metformin use and anemia risk in type 2 diabetes, and the time-course for this, in a randomized controlled trial (RCT) and real-world population data. Research Design and Methods: Anemia was defined as a hemoglobin measure of <11 g/dL. In the RCTs A Diabetes Outcome Progression Trial (ADOPT; n = 3,967) and UK Prospective Diabetes Study (UKPDS; n = 1,473), logistic regression was used to model anemia risk and nonlinear mixed models for change in hematological parameters. In the observational Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) population (n = 3,485), discrete-time failure analysis was used to model the effect of cumulative metformin exposure on anemia risk. Results: In ADOPT, compared with sulfonylureas, the odds ratio (OR) (95% CI) for anemia was 1.93 (1.10, 3.38) for metformin and 4.18 (2.50, 7.00) for thiazolidinediones. In UKPDS, compared with diet, the OR (95% CI) was 3.40 (1.98, 5.83) for metformin, 0.96 (0.57, 1.62) for sulfonylureas, and 1.08 (0.62, 1.87) for insulin. In ADOPT, hemoglobin and hematocrit dropped after metformin initiation by 6 months, with no further decrease after 3 years. In UKPDS, hemoglobin fell by 3 years in the metformin group compared with other treatments. At years 6 and 9, hemoglobin was reduced in all treatment groups, with no greater difference seen in the metformin group. In GoDARTS, each 1 g/day of metformin use was associated with a 2% higher annual risk of anemia. Conclusions: Metformin use is associated with early risk of anemia in individuals with type 2 diabetes, a finding consistent across two RCTs and replicated in one real-world study. The mechanism for this early fall in hemoglobin is uncertain, but given the time course, is unlikely to be due to vitamin B12 deficiency alone

A Prograde, Low-Inclination Orbit for the Very Hot Jupiter WASP-3b

We present new spectroscopic and photometric observations of the transiting exoplanetary system WASP-3. Spectra obtained during two separate transits exhibit the Rossiter-McLaughlin (RM) effect and allow us to estimate the sky-projected angle between the planetary orbital axis and the stellar rotation axis, lambda = 3.3^{+2.5}_{-4.4} degrees. This alignment between the axes suggests that WASP-3b has a low orbital inclination relative to the equatorial plane of its parent star. During our first night of spectroscopic measurements, we observed an unexpected redshift briefly exceeding the expected sum of the orbital and RM velocities by 140 m/s. This anomaly could represent the occultation of material erupting from the stellar photosphere, although it is more likely to be an artifact caused by moonlight scattered into the spectrograph.Comment: 23 pages, 4 figures, Accepted for publication in The Astrophysical Journal, Replacement includes revised citation